The objective of this proposal is to determine if the immune system plays an etiologic role in alcohol induced liver injury, particularly alcoholic hepatitis. We will evaluate both cellular and humoral immune function in serious alcohol related liver disease and examine their role in mediating liver injury. Thus, these studies will focus in part on the properties and reactivity of T-lymphocytes. Additionally, experiments will be performed to explore the effects of external factors such as circulating serum inhibitory substances which may influence T-lymphocyte reactivity. Comparisons will be made to other types of acute and chronic liver diseases. We will examine the mechanisms of B-lymphocyte stimulation and activity and its control in the pathogenesis of the frequently observed hypergammaglobulinemia associated with alcoholic hepatitis and cirrhosis. Finally our recent studies have shown a striking incidence of high titer circulating immune complexes in alcoholic hepatitis by two different techniques. We now wish to characterize the physical properties of these immune complexes and in paticular perform studies aimed at identifying the antigenic composition. Correlations will be made to the clinical, biochemical and histologic stages of the patient's disease. The importance of these complexes and their deposition in the liver is under intensive investigation since they appear capable of activating the complement system both in vivo and in vitro.